1 Forskning og gerontologi Længere levetid og sund aldring DSAM’s årsmøde Trinity Hotel og Konferencecenter, Snoghøj, 3. oktober 2008 Bernard Jeune DANSK CENTER FOR ALDRINGSFORSKNING SYDDANSK UNIVERSITET

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3 Rembrandt år 28 år34 år 50 år51 år52 år53 år 62 år63 år 44 år 46 år 62 år 55 år

Selvportræt som Zeuxis Selvportræt Rembrandt 1669 (ca. 62 år)

5 Aldring Mekanisk Plastisk Programmeret Foranderlig

6 1990’ernes nye opdagelser omkring aldring og levetid  1. Tilsynekomsten af Jeanne Calment og andre længelevere  2. Afdæmpning i dødeligheden ved meget høje aldre  3. Betydelig livsforlængelse i dyremodeller

7 Christian Mortensen 16/ – 25/ De længstlevende Jeanne Calment 21/ – 4/8 1997

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9 Dyremodeller Saccharomyce s cerevisiae Caenorhabditis elegans Drosophila melanogaste r Fischer 344 Rat Mouse Rhesus Monkey

10 Caenorhabditis elegans (den lille rundorm) C. elegans bliver voksen i løbet af 3 dage, lægger alle sine æg i de første 3-4 dage af sit voksenliv, og lever derefter videre ca. 10 dage (middellevetid dage). Den udvoksede C. elegans er hermafrodit, består af 959 somatiske celler, og 6 kromosomer med gener.

11 C. elegans med lange levetider C. elegans med lange levetider (efter forskellige manipulationer) Arates-Oliveira et.al.,SCIENCE, 2003 daf-2 mutation inhibit insulin/IGF-1 signaling daf-2 RNAi reduce daf-2 activity e1368 mutants are long-lived daf2 mutants which are quite active for most of their life (not lethargic and dauer-like as other daf2 mutants)

12 Aldring hos Rhesus-aber Roth et.al.,SCIENCE, 2004 A En 19-årig han-abe på normal diæt. Vægt 13,6 kg B En 19-årig han-abe på smalkost. Vægt 7,9 kg C 38-årig han-abe på smalkost de sidste 17 år. Vægt 6.8 kg

13 Kaloriebegrænsning i Biosphere 2 Roy Walford efter 15 måneder i Biosphere 2 68 kg54kg Significantly Altered Parameters Walford et al., J Gerontol Bio Sci, 2002

14 Norway New Zealand Iceland Sweden Japan The Netherlands Switzerland Australia Oeppen and Vaupel, SCIENCE, 2002 Verdensrekord i levetid Verdensrekord i levetid (for kvinder )

15 Forventet levetid for mænd og kvinder i Danmark

16 Fries’ hypothesis on Compression of Morbidity Fries JF. Aging, Natural Death, and the Compression of Morbidity. N Eng J Med 1980: 303: Morbidity Survival Compression of Morbidity

17 Compression of Morbidity Possible future scenarios Compression of Morbidity Fries JF. Measuring and Monitoring Success in Compressing Morbidity. Ann Intern Med. 2003; 139:

18 Life expectancy at age 65 in Denmark The stagnation period

19 The Danish Health Interview Surveys Random samples of Danes aged 16 or more including people living in institutions. Professionals from the Danish National Institute of Social Research visited and interviewed: 1987: 864 aged 65+ (76.5%) 1994: 827 aged 65+ (68.5%) 2000: 3,015 aged 65+ (70.2%) 2005: 3,012 aged 65+ (63.9%) Jeune et al. Eur J Ageing 2008 (in press)

20 Life expectancy at age 65 in 1987, 1994, 2000 and 2005: expected lifetime with and without long-standing illness in DK MenWomen without long-standing illness Expected lifetime with long-standing illness Jeune et al. Eur J Ageing 2008 (in press)

21 Life expectancy, expected lifetime with and without long-standing, limiting illness at age 65 in Denmark in 1994, 2000 and 2005 without long-standing, limiting illness Expected lifetime with long-standing, limiting illness Men Women Jeune et al. Eur J Ageing 2008 (in press)

22 Life expectancy at age 65 in 1987, 1994, 2000 and 2005: expected lifetime with and without mobility limitations in DK without mobility limitations Expected lifetime with mobility limitations Men Women Jeune et al. Eur J Ageing 2008 (in press)

23 Life expectancy, expected lifetime in self-rated good or poor health at age 65 in Denmark in 1987, 1994, 2000 and MenWomen with good health Expected lifetime with fair or poor health Jeune et al. Eur J Ageing 2008 (in press)

24 Centenarians in Denmark

25 The Study of Danish Centenarians Birth cohort Baseline survey at age 100 and followed annually until death The Danish 1905 Cohort Survey Birth cohort 1905 Baseline survey at age 92 and followed bi-annually until age years Two nationwide studies of Danish centenarians

26 Number of Danish centenarians Females Males Calendar year Count

27 The two Danish centenarian studies 1895-Cohort 1905-Cohort (75%) 225 (62%) 256 Mini Mental State Examination (MMSE) Basic ADL (Katz ADL) Physical ADL (Avlund´s PADL) Hospitalization, morbidity, self-reported health.

28 Prevalence of selected hospital diagnoses During 18 years (aged years) of 100-y-old Danes born in 1895 and 1905 Engberg et al. J Gerontol Med Sci, 2008 (in press)

29 Prevalence of selected hospital diagnoses During 18 years (aged years) of 100-y-old Danes born in 1895 and 1905 Engberg et al. J Gerontol Med Sci, 2008 (in press)

30 Number and proportions of Basic Activities of Daily Living performed independently, by women Women Birth cohort1895 cohort1905 cohort BADLs - performed independently, n (%) n = 162n = 189 Non-disabled Moderately disabled Severely disabled 16 ( 9.9) 67 (41.4) 79 (48.8) 39 (20.6) 81 (42.9) 69 (36.5) p-valuep = Engberg et al, J Gerontol Med Sci, 2008 (in press)

31 Proportion of female centenarians Proportion of female centenarians Independent in activities of daily living Engberg et al. J Gerontol Med Sci, 2008 (in press) Data from two birth cohorts 10 years apart ( )

32 Proportion of female centenarians Proportion of female centenarians Independent in activities of daily living Engberg et al. J Gerontol Med Sci, 2008 (in press) Data from two birth cohorts 10 years apart ( )

33 MMSE scores by cohort MMSE scores by cohort Tested by MMSE156/207 (75)176/225 (78) MMSE-Median 20 [ ]20 [ ] MMSE: n = 156n = (28.9)56 (31.8) (33.3)51 (29.0) (37.8)69 (39.2) Engberg et.al., Dement Geriatr Cogn Disord, 2008

34 The Danish 1905 Cohort 3,600 2,262 (63%) 1,086 (78%) 437 (77%) 166 (74%) August 1th ,338 Drop-outs 314 Drop-outs 127 Drop-outs 58 Drop-outs died 522 died 213 died

35 ♂ ♀ ♂ + ♀ : :30 1:10 1:15 92 years – half way to 100

36 Predictors of Mortality among Females from the Danish 1905-Cohort Survey (18 months follow-up) VariableReference – best group (categories)Adjusted HR (CI) ADL-scale (5 items)Not disabled (3)1.59 ( ) MMSE-categories23-30 Points (3)1.37 ( ) Body Mass Index>=28 (3)1.29 ( ) Self-rated HealthExcellent (4)1.21 ( ) Handgrip (kg)First quartile (5)1.14 ( ) (Adjusted Hazard Ratios (HR) and 95% Confidence Interval (CI), N=1,670) No association with: Marital status, Education, Smoking, Use of alcohol, Number of self reported diseases. Nybo et.al., JAGS, 2003

37 Independence in the 1905-Cohort Christensen et al. PNAS Early Edition 2008

38 Christensen et al. PNAS Early Edition 2008 Independence in the 1905-Cohort

39 Average lifetime in self-rated good, fair and poor health Average lifetime (years) Self-rated health Good health Fair health Poor health Men Women Health state was inestimable for 0.18 years for men and 0.41 years for women. * Estimated by replacing missing values for a person by the best and worst reported health at the other interviews for that person. Between ages 92 and 100 for Danes born in 1905 and followed up until 2006 Brønnum-Hansen et al. Age and Ageing (In Press)

40 Average lifetime (years) Physically dependence IndependentDependent Men Women Health state was inestimable for years for men and years for women. * Estimated by replacing missing values for a person by the best and worst reported health at the other interviews for that person. Between ages for Danes born in 1905 and followed up until 2006 Brønnum-Hansen et al. Age and Ageing (In Press) Average lifetime in physical independence

41 Average lifetime in physical independence and without cognitive impairment Average lifetime (years) Cognitive functioning No impairment Mild or severe impairment Men Women Health state was inestimable for years for men and 0.02 years for women. * Estimated by replacing missing values for a person by the best and worst reported health at the other interviews for that person. Between ages for Danes born in 1905 and followed up until 2006 Brønnum-Hansen et al. Age and Ageing (In Press)

42 The probability of surviving to age 90 The Physicians’ Health Study Healthy men (mean age 72) followed for 25 years Looking at 5 key adverse factors: Smoking, Diabetes, Obesity, Hypertension, and Sedentary lifestyle The probability of surviving to age 90 All 5 adverse factors: 4% Zero adverse factors: 54% Yates et al. 2008

43 Compression of Morbidity or Disability? Source: Fries JF. Aging, Natural Death, and the Compression of Morbidity. N Eng J Med 1980: 303: Disability Survival Compression of Morbidity Compression of disability

44 Det aldrende samfund ” En samfundsudvikling med længere levetid og faldende eller vedvarende lav fødselshyppighed, der fører til en ændret befolkningssammensætning med et stigende antal ældre i forhold til både antallet af børn og unge og antallet af personer i den erhvervsaktive alder.” Det Strategiske Forskningsråd. Det aldrende samfund 2030, februar 2006

45 Antal personer Antal personer under 15 år, over 65 og 80 år

46 Aldersfordelingen i Danmark Aldersfordelingen i Danmark

47 Det alderskonstruerede vs det aldersintegrerede samfund Kilde: Baggrundsnotater. Det Strategiske Forskningsråd. Det aldrende samfund Februar 2006

48 Det aldersintegrerede samfund De tre hovedområder Sund aldring med god funktionsevne og bedre udnyttelse af de nye teknologiske muligheder Aldersintegreret arbejdsmarked med bedre muligheder for senkarriere, livslang læring og fleksibel forbliven i erhvervsaktivitet Udvikling af den samfundsmæssige sammenhængskraft på tværs af generationer, køn og etnicitet Kilde: Det Strategiske Forskningsråd. Det aldrende samfund 2030, 2006

49 Faktorer der styrker eller forringer ældres funktionsevne Faktorer, der styrker:Faktorer, der forringer: n Fysisk aktivitet n Rygestop n Stressreduktion n Alsidig og tilstrækkelig kost n Hjernegymnastik n Tidlig diagnostik n Bedre behandling n Funktionskriterier n Sociale netværk og omsorg n Forebyggende hjemmebesøg n Fysisk inaktivitet n Rygning n Stressudvikling n Ensidig kost og højt kalorieindtag n Kognitiv passivitet n Sen diagnostik n Multisygdom n Aldersgrænser n Øget social ulighed n Negative ældrebilleder Kilde: Baggrundsnotater. Det Strategiske Forskningsråd. Det aldrende samfund 2030, februar 2006

50 Christensen et al. PNAS Early Edition 2008 Chris Chris Mortensen Jeanne Calment 122 år * † 115 år * †

51 Presseomtale af PNAS-artikel

52 Ongoing research  The 1905-cohort alive in 1977 (N=39,945)  European Challenge of Healthy Ageing (ECHA)  GEnetics of Healthy Ageing (GEHA)  Long Life Family Study (LLFS)

53 Six Long-Living Danish Sisters

54 De tre generationer Jacob JORDAENS ( ): As the Old Sang the Young Play Pipes, 1638 Oil on canvas, 192 x 120 cm, Koninklijk Museum voor Schone Kunsten, Antwerp

55 Seks generationer af Sarah Knauss’ familie Sarah Knauss 24/ – 30/ Sarah Knauss (115), Kitty Sullivan (92), Robert Butz (70), Kathy Jacoby (46), Kristina Patton (24), Bradley (0)

56 Co-authors Karen Andersen-Ranberg Henrik Brønnum Hansen Kaare Christensen Henriette Engberg Matt McGue Hanne Nybo Hans Christian Petersen Inge Petersen James W. Vaupel